Guselkumab treatment in patients with active psoriatic arthritis: effectiveness compared to placebo
Näytönastekatsaukset
10.11.2021
Level of evidence: A
Subcutaneous guselkumab treatment at the dose of 100 mg every 4 or 8 weeks, when compared to placebo, increases the proportion of patients with active psoriatic arthritis achieving the ACR20 response at week 24 (52–64 % vs. 18–33 %). Most adverse events seem to be mild and the number of adverse events seems to be equal to placebo.
The proportion of patients with active psoriatic arthritis and treated with guselkumab achieving the ACR50 and ACR 70 response at week 24 seems to be higher compared to patients treated with placebo.
| Ref. | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| RCT=randomized controlled trial. Sc. = subcutaneous injection ARC20=20% improvement in signs and symptoms of psoriatic arthritis according to American College of Rheumatology criteria. Minimal disease activity= fulfilling at least five of the following seven criteria: tender joint count 1 or less, swollen joint count 1 or less, PASI score 1 or less, patient pain VAS score 15 or less, patient global disease activity VAS score 20 or less, HAQ-DI score 0·5 or less, and tender entheseal points 1 or less. | |||||
| «Deodhar A, Gottlieb AB, Boehncke WH ym. Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. Lancet 2018;391:22»1 | RCT, phase 2a | 149 adult patients with moderate-to-severe psoriatic arthritis. Previously inadequate response to standard therapies (9% TNFi-exposed) | Guselkumab 100 mg sc. vs. placebo at weeks 0, 4, and then every 8 weeks up to week 20 | Primary: ACR20 at week 24; Secondary: ACR20 at week 16, ACR50, ACR70, and PASI75 at week 24, adverse events | Low |
| «Deodhar A, Helliwell PS, Boehncke WH ym. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFa inhibitor treatment (DISCOVER-1): a double-blind»2 | RCT | 381 adult patients with active psoriatic arthritis, including those who were previously treated with one or two TNF inhibitors (~31 %) | Guselkumab 100 mg sc. every 4 weeks; guselkumab sc. 100 mg at weeks 0, 4, then every 8 weeks vs. placebo sc. | Primary: ACR20 at week 24. Secondary: ACR50, ACR70, DAS28-CRP, IGA, HAQ-DI, enthesatis, dactulitis, SF-36, PASI75-100, minimal disease activity, adverse events | Low |
| «Mease PJ, Rahman P, Gottlieb AB ym. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet 2020;395:11»3 | RCT | 741 adult biologic-naive patients with active psoriatic arthritis | Guselkumab 100 mg sc. every 4 weeks; guselkumab sc. 100 mg at weeks 0, 4, then every 8 weeks vs. placebo sc. | Primary: ACR20 at week 24. Secondary: ACR50, ACR70, DAS28-CRP, IGA, HAQ-DI, enthesatis, dactulitis, SF-36, PASI75-100, minimal disease activity, adverse events | Low |
| Reference | Comments |
|---|---|
| «Deodhar A, Gottlieb AB, Boehncke WH ym. Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. Lancet 2018;391:22»1 | A phase 2a multicenter international study. Patients were permitted to use methotrexate, corticosteroids or NSAIDs. Escape to open-label ustekinumab if less than 5 % improvement at week 16 (guselkumab 10 %, placebo 35 %). These were defined as non-responders for ACR. The patients in guselkumab group seemed to have more severe plaque psoriasis and more dactylitis or entesitis. 59 % of placebo group crossed over to guselkumab at week 24 and guselkubam group received placebo at this point to maintain masking. The study was funded by Jansen Research & Development. |
| «Deodhar A, Helliwell PS, Boehncke WH ym. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFa inhibitor treatment (DISCOVER-1): a double-blind»2 | A phase 3 randomized, double-blind, placebo controlled, multicenter trial (86 sites, 13 countries). Adults with active psoriatic arthritis (at least three swollen and three tender joints, and C-reactive protein ≥ 0.3 mg/dL) despite standard therapies. Eligibility: inadequate response to or intolerance of standard treatment for psoriatic arthritis. About 30% of study participants could have previously received one or two TNF inhibitors. Patients were permitted to continue use of stable doses of one selected nonbiologic DMARD, oral corticosteroids, and NSAIDs or other analgesics. Patients were randomized in computer-generated permuted blocks and stratified by baseline DMARD and previous TNF inhibitor use. To ensure blinding the patients in each treatment group received the same number of injections at the same timepoints. 3/4/12 patients discontinued the treatment (in all 5 %). At week 16, all patients with less than 5% improvement in both swollen and tender joint counts were eligible for early escape: number of eligible patients in the groups were 3(2 %)/4 (3 %)/24 (19 %). Approximately half of the patients were women, mean duration of psoriatic arthritis was 7 years. A few numerical imbalances were observed in baseline characteristics (IGA, presence of dactylitis). The study was funded by Jansen Research & Development. |
| «Mease PJ, Rahman P, Gottlieb AB ym. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet 2020;395:11»3 | A phase 3 randomized, double-blind, placebo controlled, multicenter trial (118 sites, 13 countries). Adults with biologic-naive patients with active psoriatic arthritis (at least five swollen and five tender joints, and C-reactive protein ≥ 0.6 mg/dL) and inadequate response to standard therapies. Patients were randomized in computer-generated permuted blocks and stratified by baseline disease-modifying antirheumatic drug use and C-reactive protein concentration. Patients were permitted to continue use of selected standard treatments, including NSAIDs or other analgesics. To ensure blinding the patients in each treatment group received the same number of injections at the same timepoints. 9/8/6 patients discontinued the treatment (in all 3%). At week 16, all patients with less than 5% improvement in both swollen and tender joint counts were eligible for early escape: number of eligible patients in the groups were 12 (5%)/13 (5%)/38 (15%). Nearly half of the patients were women, mean duration of psoriatic arthritis was 5,5 years. Modest numerical differences were observed between the guselkumab and placebo groups for the proportions of men, severity of psoriasis assessed by the PASI score, and presence of dactylitis and enthesitis at baseline. The study was funded by Jansen Research & Development. |
Results
| Reference | Number of patients (I/C) | Follow-up time (weeks) | Absolute number of events (%) I | Absolute number of events (%) C | Absolute difference vs. placebo (95 % CI) |
|---|---|---|---|---|---|
| I= intervention; C=comparison; CI=confidence interval | |||||
| «Deodhar A, Gottlieb AB, Boehncke WH ym. Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. Lancet 2018;391:22»1 | 100/49 | 24 | 34 (34) | 5 (10) | 23.8 % (11.3–36.3) |
| «Deodhar A, Helliwell PS, Boehncke WH ym. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFa inhibitor treatment (DISCOVER-1): a double-blind»2 | 128/127/126 | 24 | 4 week: 46 (36) 8 week: 38 (30) | 11 (9) | 27 % (18–37) 21 % (12–31) |
| «Mease PJ, Rahman P, Gottlieb AB ym. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet 2020;395:11»3 | 246/248/247 | 24 | 4 week: 81 (33) 8 week: 78 (31) | 35 (14) | 19 % (12–26) 17 % (10–24) |
| Level of evidence: moderate The quality of evidence is downgraded due to study imprecision (wide confidence interval). | |||||
| Reference | Number of patients (I/C) | Follow-up time (weeks) | Absolute number of events (%) I | Absolute number of events (%) C | Absolute difference vs. placebo (95% CI) |
|---|---|---|---|---|---|
| I=intervention; C=comparison; CI=confidence interval; AE=adverse event, NA= not available | |||||
| «Deodhar A, Gottlieb AB, Boehncke WH ym. Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. Lancet 2018;391:22»1 | 100/49 | 24 | At least one AE 36 (36) Serious AE 1 (1) | At least one AE 16 (33) Serious AE 1 (2) | NA |
| «Deodhar A, Helliwell PS, Boehncke WH ym. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFa inhibitor treatment (DISCOVER-1): a double-blind»2 | 128/127/12 | 24 | 4 week: At least one AE 77 (55) Serious AE 0(0) 8 week: At least one AE 68(54) Serious AE 4 (3) | At least one AE 75 (60) Serious AE 5 (4) | NA |
| «Mease PJ, Rahman P, Gottlieb AB ym. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet 2020;395:11»3 | 246/248/247 | 24 | 4 week: At least one AE 113 (46) Serious AE 8 (3) 8 week: At least one AE 114 (46) Serious AE 3 (1) | At least one AE 100 (41) Serious AE 7 (3) | NA |
| Level of evidence: low The quality of evidence is downgraded due to study imprecision. | |||||
References
- Deodhar A, Gottlieb AB, Boehncke WH ym. Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. Lancet 2018;391:2213-2224 «PMID: 29893222»PubMed
- Deodhar A, Helliwell PS, Boehncke WH ym. Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFa inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet 2020;395:1115-1125 «PMID: 32178765»PubMed
- Mease PJ, Rahman P, Gottlieb AB ym. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet 2020;395:1126-1136 «PMID: 32178766»PubMed